Systemic Lupus Erythematosus (SLE) is a multifaceted autoimmune disorder characterized by autoantibody production and immune complex deposition in various tissues. Photosensitivity, observed in a substantial subset of SLE patients, involves exacerbated responses to ultraviolet (UV) exposure, triggering cutaneous flare-ups. The pathogenesis of photosensitivity involves the accumulation of apoptotic keratinocytes, which release SLE-associated autoantigens upon UV exposure. This study investigates whether heterozygous major histocompatibility complex class II (MHC-II) alleles, associated with SLE susceptibility, enhance the presentation of apoptotic keratinocyte antigens to T cells. Utilizing the parental New Zealand Black (NZB) and the NZB/New Zealand White F1 (NZB/W F1) mouse strains, both characterized by different susceptibilities to developing SLE-like disease, the role of heterozygous MHC-II alleles was explored. The NZB strain, possessing homozygous MHC-II alleles (I-A^d/d), develops hemolytic anemia, while the NZB/W F1 strain, harboring heterozygous MHC-II alleles (I-A^d/u), mirrors key aspects of human SLE. The findings of this study shed light on the interplay between MHC-II allele heterozygosity and apoptotic keratinocyte antigen presentation, offering a novel perspective on the contribution of MHC-II alleles to SLE pathogenesis. Enhanced understanding of these mechanisms may pave the way for targeted interventions aimed at modulating antigen presentation and mitigating the severity of SLE-associated photosensitivity and inflammation.